# Preserved Ejection, Lost Rhythm: A Narrative Review of the Pathophysiology and Management of Heart Failure with Preserved Ejection Fraction and Concomitant Atrial Fibrillation

## TL;DR

Heart failure with preserved ejection fraction and atrial fibrillation often coexist, worsen each other, and require tailored treatment strategies to improve patient outcomes.

## Contribution

This paper reviews the pathophysiology and management of the overlapping conditions HFpEF and AF, emphasizing novel therapeutic strategies and clinical approaches.

## Key findings

- SGLT2 inhibitors consistently reduce HF hospitalizations and AF burden in HFpEF-AF patients.
- Catheter ablation may improve quality of life and exercise hemodynamics, though evidence remains inconsistent.
- Early rhythm control and risk-factor modification are critical for managing the HFpEF-AF overlap syndrome.

## Abstract

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) coexist in 40–60% of cases and mutually reinforce each other through adverse electrical, cellular, and functional remodelling. There is considerable overlap in signs and symptoms, and diagnosis may be challenging due to nonspecific clinical presentations and chronic course. AF is clearly linked with worsening morbidity and mortality in HFpEF with higher rates of HF hospitalizations, HF progression, stroke, systemic embolism, and all-cause death. Optimal management of HFpEF-AF patients requires aggressive treatment of comorbidities and risk factor modification. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated consistent benefit with respect to HF hospitalizations, symptoms and exercise haemodynamics, and potential to reduce AF burden. Gastric inhibitory polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) agonists, mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and statins may provide benefit in selected phenotypes, though evidence remains heterogeneous. A rhythm control strategy in the early clinical course of HFpEF might be a reasonable strategy to improve symptoms and delay both AF and HFpEF disease progression. Catheter ablation appears to improve exercise haemodynamics and quality of life, and observational data suggest it may reduce mortality and HF hospitalization, though current evidence is inconsistent and not yet definitive. Emerging device-based and molecular therapies could represent promising avenues for future research. Overall, early detection of AF, comprehensive risk-factor modification, and tailored rhythm-control strategies are central to improving outcomes in the HFpEF-AF overlap syndrome.